Overexpression of D-type cyclins, E2F-1, SV40 large T antigen and HPV16 E7 rescue cell cycle arrest of tsBN462 cells caused by the CCG1/TAF(II)250 mutation

Oncogene. 1999 Mar 11;18(10):1797-806. doi: 10.1038/sj.onc.1202508.

Abstract

tsBN462 cells, which have a point mutation in CCG1/TAF(II)250, a component of TFIID complex, arrest in G1 at the nonpermissive temperature of 39.5 degrees C. Overexpression of D-type cyclins rescued the cell cycle arrest of tsBN462 cells, suggesting that the cell cycle arrest was through Rb. Consistent with this, overexpression of E2F-1, whose function is repressed by the hypophosphorylated form of Rb, also rescued the cell cycle arrest. Moreover, expression of the viral oncoproteins SV40 large T antigen and HPV16 E7, which both bind Rb and inactivate its function, rescued the cell cycle arrest, whereas HPV16 E6 did not. Mutation of the Rb-binding motif in E7 abrogated its ability to rescue the cell cycle arrest. Expression of exogenous cyclin D1, SV40 large T antigen or CCG1/TAF(II)250 increased cyclin A expression at 39.5 degrees C. Coexpression of HPV16 E7 and adenovirus E1b19K, which blocks apoptosis, rescued the proliferation of tsBN462 cells at 38.5 degrees C. To investigate the mechanism underlying the lack of cyclin D1 expression, deletion analysis of cyclin D1 promoter was performed. The 0.15 kbp cyclin D1 core promoter region, which lacks any transcription factor binding motifs, still exhibited a temperature-sensitive phenotype in tsBN462 cells suggesting that CCG1/TAF(II)250 is critical for the function of the cyclin D1 core promoter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Antigens, Polyomavirus Transforming / metabolism*
  • Carrier Proteins*
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cell Division
  • Cell Line
  • Cricetinae
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • G1 Phase
  • Histone Acetyltransferases
  • Humans
  • Mutagenesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus E7 Proteins
  • Phenotype
  • Promoter Regions, Genetic
  • Retinoblastoma-Binding Protein 1
  • TATA-Binding Protein Associated Factors*
  • Temperature
  • Transcription Factor DP1
  • Transcription Factor TFIID*
  • Transcription Factors / metabolism*

Substances

  • Antigens, Polyomavirus Transforming
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Retinoblastoma-Binding Protein 1
  • TATA-Binding Protein Associated Factors
  • Transcription Factor DP1
  • Transcription Factor TFIID
  • Transcription Factors
  • oncogene protein E7, Human papillomavirus type 16
  • Cyclin D1
  • Histone Acetyltransferases
  • TATA-binding protein associated factor 250 kDa